IdA stringlengths 6 21 | IdB stringlengths 6 21 | labels float64 0 2 | mechanism stringclasses 40 values | effect stringclasses 10 values | score float64 0.1 0.99 ⌀ | sentence stringlengths 10 1.63k ⌀ | signor_id stringlengths 12 14 |
|---|---|---|---|---|---|---|---|
Q9H410 | Q96GD4 | 0 | phosphorylation | down-regulates | 0.653 | To determine whether the combinatorial regulation of the kmn network by aurora b observed in vitro is critical to controlling kinetochore-microtubule attachments in vivo, we next investigated the effect of the phosphomimetic (to aspartate) and nonphosphorylatable (to alanine) mutants of dsn1, knl1, and ndc80 in vertebrate cells. We predicted that both types of mutations in critical phosphorylation sites would affect chromosome segregation, since preventing the inactivation of inappropriately attached kinetochores by aurora b (in the nonphosphorylatable mutant) or constitutively inactivating this attachment (in the phosphomimetic mutant). | SIGNOR-165546 |
P49768 | P49755 | 0 | binding | up-regulates | 0.653 | Here we report that tmp21, a member of the p24 cargo protein family, is a component of presenilin complexes and differentially regulates gamma-secretase cleavage | SIGNOR-146364 |
P19174 | P04629 | 0 | phosphorylation | up-regulates | 0.652 | The nerve growth factor (ngf) receptor/trk associated with and phosphorylated phospholipase c gamma (plc gamma) | SIGNOR-38538 |
P40189 | O14543 | 0 | binding | down-regulates activity | 0.652 | SOCS3 binds specific receptor-JAK complexes to control cytokine signaling by direct kinase inhibition. The inhibitory protein SOCS3 plays a key part in the immune and hematopoietic systems by regulating signaling induced by specific cytokines. SOCS3 functions by inhibiting the catalytic activity of Janus kinases (JAKs) that initiate signaling within the cell. | SIGNOR-255328 |
Q12778 | P24941 | 0 | phosphorylation | down-regulates | 0.652 | Cdk2 specifically phosphorylated foxo1 at serine-249 (ser249) in vitro and in vivo. Phosphorylation of ser249 resulted in cytoplasmic localization and inhibition of foxo1. | SIGNOR-150028 |
P41145 | P01189 | 0 | chemical activation | up-regulates activity | 0.652 | Accordingly, for the OTDP, the binding affinity and activity of a large number of opiate compounds have been tested at μ-, δ-, and κ-opiate receptors. Binding studies were originally conducted in guinea pig brain membranes, and subsequent studies have been carried out in CHO cells transfected with human receptors. Table 7 shows a biochemical method for determining activity and potency of opioid compounds, stimulation of [35S]GTPγS binding in membranes from cells transfected with human μ, δ, or κ receptors. | SIGNOR-258410 |
O43353 | Q13490 | 0 | polyubiquitination | up-regulates activity | 0.652 | CIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4).Together, our results demonstrate that depleting cIAP1/2 inhibits RIP1-4 mediated NF-kB activation without affecting RIP auto-phosphorylation. | SIGNOR-272712 |
Q9UJT9 | Q96ME1 | 0 | binding | down-regulates quantity by destabilization | 0.652 | F-box protein Fbxl18 mediates polyubiquitylation and proteasomal degradation of the pro-apoptotic SCF subunit Fbxl7.. Here, we identified that an orphan F-box protein, Fbxl18, targets Fbxl7 for its polyubiquitylation and proteasomal degradation. Lys 109 within Fbxl7 is an essential acceptor site for ubiquitin conjugation by Fbxl18. | SIGNOR-272448 |
O75051 | Q13214 | 0 | binding | up-regulates activity | 0.652 | We provide evidence suggesting that, in endothelial cells and glioblastoma cells, plexin-A4 is a required component of both Sema3A and Sema3B receptor complexes and inhibition of its expression nullifies both Sema3A and Sema3B signaling. The specificity for Sema3A or Sema3B is determined by the presence of plexin-A1 in Sema3A receptors and plexin-A2 in Sema3B receptors, and silencing each abrogates signaling by the appropriate semaphorin. | SIGNOR-261812 |
P50391 | P01298 | 0 | binding | up-regulates | 0.652 | Human y4 bound human pp family members in i-pyy membrane binding assays with a distinctive rank order (table 1): pp > pyy > npy > npy free acid. | SIGNOR-24230 |
P23258 | Q96SN8 | 0 | binding | up-regulates activity | 0.652 | Immunoprecipitation of CDK5RAP2 specifically coprecipitated _TuRC components, as detected on immunoblots of _-tubulin and GCP3 (Figure 3A).| Perturbing CDK5RAP2 function delocalized gamma-tubulin from the centrosomes and inhibited centrosomal microtubule nucleation, thus leading to disorganization of interphase microtubule arrays and formation of anastral mitotic spindles. Together, CDK5RAP2 is a pericentriolar structural component that functions in gammaTuRC attachment and therefore in the microtubule organizing function of the centrosome. | SIGNOR-260310 |
Q9Y243 | O15530 | 0 | phosphorylation | up-regulates | 0.651 | The activation of pkbbeta and pkbgamma by pdk1 was accompanied by the phosphorylation of the residues equivalent to thr308 in pkbalpha, namely thr309 (pkbbeta) and thr305 (pkbgamma) | SIGNOR-55937 |
O75143 | P42345 | 0 | phosphorylation | down-regulates | 0.651 | Mtor phosphorylates a mammalian homologue of atg13 and the mammalian atg1 homologues ulk1 and ulk2. | SIGNOR-183965 |
Q6ZNE5 | O75385 | 0 | phosphorylation | up-regulates activity | 0.651 | ULK1 phosphorylates ATG14 at serine 29. | SIGNOR-278433 |
P17181 | P01562 | 0 | binding | up-regulates | 0.651 | The present study describes a novel type i ifn receptor having the ability to bind and respond to several subtypes of ifn-a as well as to ifn-8. This 102 kda-51 kda receptor is essential for the activity of many type i ifns, as demonstrated with anti-receptor antibodies. | SIGNOR-36622 |
P36956 | O43462 | 0 | cleavage | up-regulates activity | 0.651 | In order to activate transcription, the NH2-terminal domain of the SREBP must be released from the membrane so that it can enter the nucleus. This release has been studied most extensively for one of the SREBPs, namely, SREBP-2. However, the mechanism appears to be similar for the other SREBPs (SREBP-1a and -1c) (1). Release of the NH2-terminal domain is accomplished by a two-step proteolytic event that is regulated by sterols (3). In sterol-depleted mammalian cells, this proteolysis is initiated by the Site-1 protease (S1P), which cleaves human SREBP-2 between the Leu522-Ser523 bond in the sequence RSVL S (4). This cleavage requires formation of a complex between SREBP and SCAP, a polytopic membrane protein of the ER, and it is prevented when this complex is disrupted | SIGNOR-267499 |
O95229 | Q96GD4 | 0 | phosphorylation | up-regulates activity | 0.651 | Zwint-1 is a novel Aurora B substrate required for the assembly of a dynein-binding platform on kinetochores|During prometaphase, AurB phosphorylation of zwint-1 is required for recruitment of ZW10-, pT89 dynein-, and RZZ-dependent proteins to kinetochores. This is defective after AurB inhibition or after expression of the triple-A zwint-1 mutant. Triple-E mutant zwint-1 mimics phospho–zwint-1 in RZZ recruitment, even after AurB inhibition | SIGNOR-265010 |
Q9UBE8 | O43318 | 0 | phosphorylation | up-regulates | 0.651 | The tak1-nlk-mapk-related pathway antagonizes signalling between beta-catenin and transcription factor tcf. | SIGNOR-96425 |
P10070 | Q9Y297 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.651 | The phosphorylated gli2 protein interacts with beta-trcp, and is ubiquitinated and degraded by the proteasome | SIGNOR-146109 |
P07992 | P54727 | 0 | binding | up-regulates activity | 0.65 | GG-NER is initiated by the GG-NER specific factor XPC-RAD23B, in some cases with the help of UV-DDB (UV-damaged DNA-binding protein). TC-NER is initiated by RNA polymerase stalled at a lesion with the help of TC-NER specific factors CSA, CSB, and XAB2. Both pathways require the core NER factors to complete the excision process|The core NER dual incision reaction has been reconstituted in vitro with purified factors using XPC-RAD23B, TFIIH, XPA, RPA, XPG, and ERCC1-XPF (Aboussekhra et al. 1995; Mu et al. 1995; Araujo et al. 2000).|The core NER dual incision reaction has been reconstituted in vitro with purified factors using XPC-RAD23B, TFIIH, XPA, RPA, XPG, and ERCC1-XPF (Aboussekhra et al. 1995; Mu et al. 1995; Araujo et al. 2000). Functional studies revealed that XPC-RAD23B is the initial damage recognition factor in this system, as the presence of XPC-RAD23B is required for assembly of the other core NER factors and progression through the NER pathway both in vitro and in vivo | SIGNOR-275703 |
P05106 | Q86UX7 | 0 | binding | up-regulates activity | 0.65 | Mechanistically, Kindlin-3 can directly bind to regions of beta-integrin tails distinct from those of Talin and trigger integrin activation. We have therefore identified Kindlin-3 as a novel and essential element for platelet integrin activation in hemostasis and thrombosis|Kindlin-3 was also able to interact with the wild-type beta1 and beta3 integrin tails (Fig. 3c), in the presence and absence of Talin1 (Supplementary Fig. 3 online), and the F3 subdomain of Kindlin-3 was sufficient for this interaction and this interaction occurred in a direct manner | SIGNOR-266066 |
O43524 | P45983 | 0 | phosphorylation | up-regulates activity | 0.65 | As JNK1 phosphorylates FOXO3 at S574, 12 allowing formation of the proapoptotic species, we tested whether FOXO3 acetylation is required for the JNK1-FOXO3 interaction. | SIGNOR-280030 |
O00141 | O15530 | 0 | phosphorylation | up-regulates activity | 0.65 | PDK1 activates SGK in vitro by phosphorylating Thr256. | SIGNOR-250275 |
P10916 | Q5VT25 | 0 | phosphorylation | up-regulates activity | 0.65 | These approximately 190-kDa myotonic dystrophy kinase-related Cdc42-binding kinases (MRCKs) preferentially phosphorylate nonmuscle myosin light chain at serine 19, which is known to be crucial for activating actin-myosin contractility. | SIGNOR-250723 |
P62993 | P10721 | 0 | binding | up-regulates activity | 0.65 | We furthermore demonstrate that the adapter protein Grb2 is a specific binding partner for both phosphorylated Tyr-703 and phosphorylated Tyr-936, whereas the adapter protein Grb7 binds selectively to phosphorylated Tyr-936. | SIGNOR-248283 |
P41143 | P01189 | 0 | chemical activation | up-regulates activity | 0.65 | Accordingly, for the OTDP, the binding affinity and activity of a large number of opiate compounds have been tested at μ-, δ-, and κ-opiate receptors. Binding studies were originally conducted in guinea pig brain membranes, and subsequent studies have been carried out in CHO cells transfected with human receptors. Table 7 shows a biochemical method for determining activity and potency of opioid compounds, stimulation of [35S]GTPγS binding in membranes from cells transfected with human μ, δ, or κ receptors. | SIGNOR-258409 |
P19174 | P16234 | 0 | phosphorylation | up-regulates | 0.65 | Tyrosine phosphorylation has been shown to increase the enzymatic activity of plc-? / we show that the human pdgf ?- And ?-Receptors differ quantitatively in their abilities to associate with and phosphorylate plc-? And to stimulate inositol phosphate production. | SIGNOR-28176 |
P31391 | O00230 | 0 | binding | up-regulates | 0.65 | Cortistatin is known to bind all five cloned somatostatin receptors and share many pharmacological and functional properties with somatostatin including the depression of neuronal activity. | SIGNOR-82493 |
Q9HCM2 | Q13214 | 0 | binding | up-regulates activity | 0.65 | We provide evidence suggesting that, in endothelial cells and glioblastoma cells, plexin-A4 is a required component of both Sema3A and Sema3B receptor complexes and inhibition of its expression nullifies both Sema3A and Sema3B signaling. The specificity for Sema3A or Sema3B is determined by the presence of plexin-A1 in Sema3A receptors and plexin-A2 in Sema3B receptors, and silencing each abrogates signaling by the appropriate semaphorin. | SIGNOR-261810 |
Q99558 | Q13489 | 0 | ubiquitination | down-regulates | 0.65 | Ciap1/2 (cellular inhibitor of apoptosis 1 and 2) ubiquitinate nik for degradation. | SIGNOR-167298 |
P48023 | O95407 | 0 | binding | down-regulates | 0.65 | Tr6 specifically binds fas ligand. Tr6 may play a regulatory role for suppressing in fasl- mediated cell death. | SIGNOR-67434 |
O14641 | Q14332 | 0 | binding | up-regulates activity | 0.65 | Upon ligand binding, DVL proteins are recruited to Frizzled receptors at the plasma membrane and co-recruit cytoplasmic transducers, such as Axin, CK1 and GSK3 binding protein (GBP), presumably along with their partners, to promote ?-catenin-dependent signalling. | SIGNOR-258959 |
Q14449 | Q02763 | 0 | phosphorylation | up-regulates activity | 0.65 | Together these results suggest a role for the Grb14 SH2 domain in Tie2 mediated Grb14 signaling.|Tyrosine phosphorylation of Grb14 by Tie2. | SIGNOR-279300 |
Q12959 | Q9UQM7 | 0 | phosphorylation | down-regulates activity | 0.649 | Synapse-associated protein 97 (SAP97), a member of membrane-associated guanylate kinase protein family, has been implicated in the processes of targeting ionotropic glutamate receptors at postsynaptic sites. | We show here that SAP97 is directly associated with NR2A through its PDZ1 domain, and CaMKII-dependent phosphorylation of SAP97-Ser-232 disrupts NR2A interaction both in an in vitro pull-out assay and in transfected COS-7 cells. Moreover, expression of SAP97(S232D) mutant has effects similar to those observed upon constitutively activating CaMKII. | SIGNOR-250618 |
Q06330 | Q13642 | 0 | binding | down-regulates | 0.649 | It was demonstrated by emsa that kyot2 can form a complex with dna-bound rbp-j, but the dna-binding affinity of the kyot2rbp-j complex is greatly weakened and it exists mostly dissociated from dna | SIGNOR-54277 |
P03372 | Q15466 | 0 | binding | down-regulates | 0.649 | Our results identify shp as an inhibitor of 4-oht agonist activity in rl95-2 human endometrial carcinoma cells that express endogenous er?. We conclude that shp does not decrease er expression, but rather it is the direct interaction of shp with er that inhibits er transcriptional activity. | SIGNOR-115033 |
P10827 | P28702 | 0 | binding | up-regulates | 0.649 | Like many receptors belonging to the superfamily of steroid/thyroid nuclear receptors, thyroid hormone receptors (trs) bind to specific th-dna responsive elements (tre) upstream of target gene in heterodimeric complex with the 9-cis retinoid acid receptor (rxr | SIGNOR-81452 |
Q99570 | Q96F24 | 0 | binding | down-regulates activity | 0.649 | NRBF2 S113 and S120 phosphorylation negatively regulates autophagy. Phosphorylated NRBF2 inhibits autophagy, preferentially binds a nonautophagic form of the PtdIns3K complex consisting of PIK3C3-PIK3R4 only, and this NRBF2-associated PtdIns3K complex has low lipid kinase activity. | SIGNOR-265878 |
P52564 | Q9UL54 | 0 | binding | up-regulates activity | 0.649 | Cotransfection experiments suggested that tao2 selectively activates mek3 and mek6 but not meks 1, 4, or 7. | SIGNOR-70950 |
P01106 | Q13177 | 0 | phosphorylation | down-regulates activity | 0.649 | Here we demonstrate that Pak2 phosphorylates Myc at three sites (T358, S373, and T400) and affects Myc functions both in vitro and in vivo. | SIGNOR-278489 |
O75581 | P56703 | 0 | binding | up-regulates | 0.649 | Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. | SIGNOR-131823 |
P10275 | P49841 | 0 | phosphorylation | down-regulates activity | 0.649 | Glycogen synthase kinase-3 beta is involved in the phosphorylation and suppression of androgen receptor activity.|In particular, we showed that glycogen synthase kinase-3 beta phosphorylates the androgen receptor, thereby inhibiting androgen receptor-driven transcription. | SIGNOR-279334 |
P19174 | P04626 | 0 | binding | up-regulates | 0.649 | Activated egfr binds the sh2 domain of phospholipase c-gamma (plc-gamma), activating plc-gamma-mediated downstream signaling. | SIGNOR-20815 |
Q96T60 | P78527 | 0 | phosphorylation | up-regulates | 0.649 | We demonstrate that pnkp is phosphorylated by the dna-dependent protein kinase (dna-pk) and ataxia-telangiectasia mutated (atm) in vitro. The major phosphorylation site for both kinases was serine 114, with serine 126 being a minor site. Purified pnkp protein with mutation of serines 114 and 126 had decreased dna kinase and dna phosphatase activities and reduced affinity for dna in vitro. | SIGNOR-176020 |
O75197 | P56705 | 0 | binding | up-regulates | 0.649 | Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. | SIGNOR-131832 |
P38484 | P01579 | 0 | binding | up-regulates | 0.649 | Ifn-g Binds to the ifn-g Receptor binding subunit (ifn-gR1;receptor chain 1), a species-specific cell surface transmembrane receptor chain (41, 42). A second transmembrane protein (ifn-gR2) (43 45) is required for signal transduction | SIGNOR-31013 |
O00763 | P54646 | 0 | phosphorylation | down-regulates activity | 0.649 | The results suggest that the decrease in ACC activity during muscle contraction is caused by an increase in its phosphorylation, most probably due, at least in part, to activation of the alpha2 isoform of AMPK. | SIGNOR-250318 |
O75581 | Q9ULV1 | 0 | binding | up-regulates activity | 0.649 | Here we show that both Fz and Dvl functions are critical for Wnt-induced Lrp6 phosphorylation through Fz-Lrp6 interaction. | SIGNOR-258964 |
Q16665 | P46531 | 0 | relocalization | up-regulates activity | 0.649 | The notch intracellular domain interacts with hif-1alpha and hif-1alpha is recruited to notch-responsive promoters upon notch activation under hypoxic conditions. | SIGNOR-141315 |
Q4KMG0 | P19022 | 0 | binding | up-regulates | 0.648 | We report here that n-cadherin ligation activates p38alpha/beta in myoblasts in a cdo-, bnip-2-, and jlp-dependent manner | SIGNOR-163844 |
P15311 | P12931 | 0 | phosphorylation | up-regulates | 0.648 | Src phosphorylates ezrin at tyrosine 477 and induces a phosphospecific association between ezrin and a kelch-repeat protein family member | SIGNOR-132907 |
Q8NI17 | Q6EBC2 | 0 | binding | up-regulates | 0.648 | Here we identify a four-helix bundle cytokine we have called interleukin 31 (il-31), which is preferentially produced by t helper type 2 cells. Il-31 signals through a receptor composed of il-31 receptor a and oncostatin m receptor. | SIGNOR-125313 |
P60953 | Q5JSP0 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.648 | We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2). | SIGNOR-260553 |
A8MYZ6 | P31749 | 0 | phosphorylation | down-regulates | 0.648 | The phosphorylation of the two remaining akt-dependent sites inhibits foxo6 transcriptional activity | SIGNOR-252582 |
Q96BY7 | Q9Y484 | 0 | binding | up-regulates activity | 0.648 | WIPI4 interacts with ATG2, AMPK and ULK1. Upon starvation and AMPK activation, WIPI4-ATG2 dissociates from AMPK and ULK1 and localizes at nascent autophagosomes, potentially supporting further autophagosome maturation. | SIGNOR-268484 |
Q9Y243 | O60346 | 0 | dephosphorylation | down-regulates activity | 0.648 | The Abl kinase inhibitors and depletion of Bcr-Abl induced the expression of PHLPP1 and PHLPP2, which dephosphorylated Ser-473 on Akt1, -2, and -3, resulting in inhibited proliferation of CML cells.|Thus, Bcr-Abl represses the expression of PHLPP1 and PHLPP2 and continuously activates Akt1, -2, and -3 via phosphorylation on Ser-473, resulting in the proliferation of CML cells. | SIGNOR-248330 |
Q13485 | Q93008 | 0 | deubiquitination | up-regulates | 0.648 | Smad4 is monoubiquitinated in lysine 519 in vivo, a modification that inhibits smad4 by impeding association with phospho-smad2. Fam reverts this negative modification, re-empowering smad4 function;control of smad4 is a good way to regulate bone formation. Fam and ectodermin/tif1gamma (ecto) were reported to respectively regulate the de-ubiquitination and ubiquitination of smad4. | SIGNOR-236855 |
Q9NS23 | P01116 | 0 | binding | up-regulates activity | 0.648 | Mutant K-Ras promotes MST2 activation in two ways (i.e., by direct disruption of the inhibitory Raf-1-MST2 complex (Matallanas et al., 2008) and by forming an activating (i.e., by direct disruption of the inhibitory Raf-1-MST2 complex K-Ras-RASSF1AMST2 complex, as reported here | SIGNOR-249585 |
P29597 | Q08334 | 0 | binding | up-regulates | 0.648 | Specifically, il-10 effects the activation of jak1 (associated with the il-10 receptor ? Chain) and tyk2 (associated with the il-10 receptor ? Chain) and induces the activation of stat1, stat3, and, in some cells, stat5. | SIGNOR-68013 |
O75581 | P56705 | 0 | binding | up-regulates | 0.648 | Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. | SIGNOR-131835 |
P62834 | Q92565 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.648 | We found here that cAMP-dependent activation of Epac1 and Rap1 but not PKA is able to activate CaMKI to mediate Ser47 (S47) phosphorylation in GCM1. Epac1 and Epac2 proteins were identified as cAMP-binding proteins with guanine nucleotide exchange factor (GEF) activities for the small GTPases, Rap1 and Rap2 | SIGNOR-262682 |
O75581 | O00755 | 0 | binding | up-regulates activity | 0.648 | Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. | SIGNOR-131903 |
P53778 | P46734 | 0 | phosphorylation | up-regulates | 0.648 | Mkk3, mkk4 and mkk6 all show a strong preference for phosphorylation of the tyrosine residue of the thr-gly-tyr motifs in their known substrates sapk2a/p38, sapk3/p38 gamma and sapk4/p38 delta. we therefore examined the phosphorylation of sapk2a/p38, sapk3/p38? And sapk4/p38? By mkk3, mkk4 and mkk6, which are all known to be capable of activating these enzymes in vitro. | SIGNOR-83718 |
P84022 | Q8N2W9 | 0 | binding | down-regulates | 0.648 | Piasy binds most strongly with smad3 and also associates with other receptor-regulated smads and smad4. smad3, smad4, and piasy can form a ternary complex. Piasy does not inhibit smad complex binding to dna, but it represses smad transcriptional activity. | SIGNOR-104538 |
Q9NPG1 | P56706 | 0 | binding | up-regulates | 0.647 | Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. | SIGNOR-131978 |
Q6PKX4 | P07949 | 0 | binding | up-regulates | 0.647 | These data identify dok-6 as a novel dok-4/5-related adaptor molecule that may function in vivo to transduce signals that regulate ret-mediated processes such as axonal projection. | SIGNOR-127382 |
P22681 | O14492 | 0 | binding | up-regulates | 0.647 | Aps couples c-cbl to theinsulinreceptor, resulting in ubiquitination of theinsulinreceptor. The aps adapter protein couples theinsulinreceptor to the phosphorylation of c-cbl and facilitates ligand-stimulated ubiquitination of theinsulinreceptor. | SIGNOR-109691 |
P15172 | Q92831 | 0 | binding | up-regulates | 0.647 | Our results provide direct evidence that myod acetylation functionally activates the protein and show that both pcaf and cbp/p300 are candidate enzymes for myod acetylation in vivo | SIGNOR-81059 |
P19438 | O95429 | 0 | binding | down-regulates activity | 0.647 | It was suggested that the silencer of death domains (SODD) protein constitutively associates intracellularly with TNFR1 and inhibits the recruitment of cytoplasmic signaling proteins to TNFR1 to prevent spontaneous aggregation of the cytoplasmic death domains of TNFR1 molecules that are juxtaposed in the absence of ligand stimulation | SIGNOR-245022 |
P24844 | O75116 | 0 | phosphorylation | up-regulates activity | 0.647 | Here we found that Rho-kinase stoichiometrically phosphorylated myosin light chain (MLC). Peptide mapping and phosphoamino acid analyses revealed that the primary phosphorylation site of MLC by Rho-kinase was Ser-19, which is the site phosphorylated by MLC kinase. Rho-kinase phosphorylated recombinant MLC, whereas it failed to phosphorylate recombinant MLC, which contained Ala substituted for both Thr-18 and Ser-19. We also found that the phosphorylation of MLC by Rho-kinase resulted in the facilitation of the actin activation of myosin ATPase. | SIGNOR-261709 |
P46108 | P16234 | 0 | binding | up-regulates | 0.647 | Crk could bind to both pdgf alpha- and beta-receptors in vivo. | SIGNOR-75881 |
Q92993 | P00519 | 0 | phosphorylation | down-regulates activity | 0.647 | We present evidence that Tip60 is modified on tyrosine 327 by Abl kinase. We show that this causes functional changes in HAT activity and the subcellular localization of TIP60, which forms a complex with Abl kinase. The Tip60 mutation Y327F abolished tyrosine phosphorylation, reduced the inhibition of Tip60 HAT activity, and caused G0-G1 arrest and association with FE65. | SIGNOR-276598 |
Q9Y572 | Q13489 | 0 | polyubiquitination | up-regulates activity | 0.647 | CIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4).Together, our results demonstrate that depleting cIAP1/2 inhibits RIP1-4 mediated NF-kB activation without affecting RIP auto-phosphorylation. | SIGNOR-272714 |
P46531 | Q9Y644 | 0 | binding | up-regulates | 0.647 | We demonstrate that egf 12, a portion of the ligand-binding site, is modified with o-fucose and that this site is evolutionarily conserved. We also show that endogenous fringe proteins in chinese hamster ovary cells (lunatic fringe and radical fringe) as well as exogenous manic fringe modify o-fucose on many but not all egf repeats of mouse notch1. | SIGNOR-96561 |
P17861 | O75460 | 0 | phosphorylation | up-regulates activity | 0.647 | IRE1\u03b1 phosphorylates and activates the XBP1 transcription factor XBP1 via its kinase activity. | SIGNOR-279712 |
P27361 | P67775 | 0 | dephosphorylation | down-regulates | 0.647 | P-erk1/2 proteins were efficiently dephosphorylated in vitro by protein phosphatases 1 and 2a (pp1/2a) and mapk phosphatase 3 (mkp3). | SIGNOR-103162 |
P17861-2 | O75460 | 0 | post transcriptional regulation | up-regulates quantity by expression | 0.647 | Upon activation by oligomerization and autophosphorylation, the cytosolic RNase domain of IRE1 mediates an unconventional splicing of the mRNA of X-box-binding protein 1 (XBP1). The spliced and frameshifted transcript encodes XBP1S, a bZIP transcription factor inducing the expression of numerous UPR effector genes that enhance ER folding capacity. | SIGNOR-260183 |
P08670 | P31749 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.647 | The binding of akt (tail region) to vim (head region) results in vim ser39 phosphorylation enhancing the ability of vim to induce motility and invasion while protecting vim from caspase-induced proteolysis. | SIGNOR-252511 |
P57764 | P49662 | 0 | cleavage | up-regulates activity | 0.647 | Co-expression of GSDMD with caspase-1, 4, 5 or 11 but not apoptotic caspases (caspase-2, 8 and 9) in 293T cells induced the same cleavage of GSDMD|inflammatory caspases specifically cleave GSDMD after the 272FLTD275 (or 273LLSD276) sequence | | SIGNOR-256417 |
Q07889 | P19174 | 0 | binding | up-regulates | 0.647 | We provide evidence that sos1, a p21ras-specific guanine nucleotide exchange factor, directly binds to the sh3 domain of plc-gamma1, and that the sh3 domain of plc-gamma1 is involved in sos1-mediated p21ras activation. | SIGNOR-80024 |
P19174 | Q16620 | 0 | phosphorylation | up-regulates activity | 0.647 | Both Shc and PLCgamma1 are phosphorylated by TrkB, thereby initiating Shc/Ras/MAP kinase and PLCgamma1 signaling respectively.|We conclude that activation of pY783 PLCgamma1 is due mainly to TrkB activation in these models and that TrkB induced PLCgamma1 signaling promotes limbic epileptogenesis. | SIGNOR-279241 |
P35568 | Q05655 | 0 | phosphorylation | down-regulates activity | 0.646 | Protein kinase C Theta inhibits insulin signaling by phosphorylating IRS1 at Ser(1101). | SIGNOR-249267 |
Q9ULW2 | P56706 | 0 | binding | up-regulates | 0.646 | Wnt7b can bind to fzd1 and -10 on the cell surface and cooperatively activate canonical wnt signaling | SIGNOR-137934 |
P24844 | Q13464 | 0 | phosphorylation | up-regulates | 0.646 | Rho-kinase phosphorylates the mlc of intact myosin and activates its mgatpase activity in a gtp_?Rho-dependent manner. | SIGNOR-43031 |
Q7Z434 | Q96J02 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.646 | These data collectively indicate that AIP4 is the E3 ligase for MAVS.|We generated single substitutions (K362A, K371A or K420A) and combined point substitutions of MAVS and tested their degradation. K371A or K420A MAVS showed partial resistance to PCBP2-induced degradation (data not shown), whereas MAVS with the combined substitutions K371A and K420A (KK-AA) completely withstood the degradation | SIGNOR-260362 |
Q7Z434 | Q15366 | 0 | binding | down-regulates quantity by destabilization | 0.646 | PCBP2 mediates degradation of the adaptor MAVS via the HECT ubiquitin ligase AIP4. | SIGNOR-260360 |
Q9NPG1 | O00755 | 0 | binding | up-regulates activity | 0.646 | Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. | SIGNOR-131897 |
P04798 | P27540 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.646 | Kaempferol proved to be capable of inhibiting binding of agonist and agonist-induced formation of the AHR/ARNT DNA-binding complex and upregulation of the AHR target gene, CYP1A1. | SIGNOR-259910 |
Q13164 | Q16828 | 0 | dephosphorylation | down-regulates activity | 0.646 | However, whilst the interaction itself might be difficult to monitor, DUSP6 should still be able to promote the de-phosphorylation of ERK5 in cells if it is an ERK5 phosphatase.To test this HEK293 cells were transiently transfected with HA-ERK2 or HA-ERK5 together with EGFP-MEK1E (a constitutively active version of MEK1) or EGFP-MEK5D (a constitutively active version of MEK5).|Whilst one can envisage scenarios in which the interaction between DUSPs and their substrates might be transient, DUSP6 should still be able to promote the de-phosphorylation and inactivation of ERK5. | SIGNOR-277007 |
P29597 | P18031 | 0 | dephosphorylation | down-regulates activity | 0.646 | Upon ligand binding, IL-2R , IL-6R or LeptinR , IFN-_R , IFN-_R and PRLR or growth hormone (GH) receptor associated JAKs become activated. These JAKs mediate phosphorylation of specific tyrosine residues and recruit STATs. Activated STATs are released from the receptor and translocate to the nucleus. PTP1B dephosphorylates JAK2, TYK2 and STAT5 . The 45-kDa form of TC-PTP was shown to dephosphorylate JAK1 and JAK3 as well as STAT1, STAT3 and STAT5. | SIGNOR-134564 |
Q9UN19 | P06239 | 0 | phosphorylation | up-regulates activity | 0.646 | Src family kinases mediate receptor-stimulated, phosphoinositide 3-kinase-dependent, tyrosine phosphorylation of dual adaptor for phosphotyrosine and 3-phosphoinositides-1 in endothelial and B cell lines|yrosine phosphorylation of DAPP-1 appears important for appropriate intracellular targeting and creates a potential binding site for Src homology 2 domain-containing proteins. | SIGNOR-249373 |
P23458 | P29350 | 0 | dephosphorylation | down-regulates | 0.646 | We find, for the first time, that shp-1 down-regulates the level of tyk2 kinase in h9 cells and of jak1 kinase in htb26 cells, by accelerating their degradation. | SIGNOR-119197 |
Q99683 | P31751 | 0 | phosphorylation | down-regulates activity | 0.646 | Akt2 interacts with and phosphorylates ask1 at ser-83 resulting in inhibition of its kinase activity | SIGNOR-100588 |
O14733 | O43318 | 0 | phosphorylation | up-regulates activity | 0.645 | Upon TNFα stimulation, MEKK1, ASK1, and TAK1 phosphorylate and activate MKK7, which in turn activates JNK | SIGNOR-274146 |
O43815 | Q9P2B4 | 0 | binding | up-regulates activity | 0.645 | Although CTTNBP2 and CTTNBP2NL are different in terms of tissue and subcellular distribution, our data indicate that, similar to CTTNBP2NL, CTTNBP2 associates with members of the striatin family, namely striatin and zinedin. Moreover, CTTNBP2 is critical for the distribution of striatin and zinedin in dendritic spines. The role of CTTNBP2 in the regulation of the synaptic distribution of striatin and zinedin suggests that CTTNBP2 regulates synaptic signaling through PP2A. | SIGNOR-261702 |
O15169 | Q9NTX7 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.645 | Here, we identify RNF146, a RING-domain E3 ubiquitin ligase, as a positive regulator of Wnt signalling. RNF146 promotes Wnt signalling by mediating tankyrase-dependent degradation of axin. Mechanistically, RNF146 directly interacts with poly(ADP-ribose) through its WWE domain, and promotes degradation of PARsylated proteins. Using proteomics approaches, we have identified BLZF1 and CASC3 as further substrates targeted by tankyrase and RNF146 for degradation. | SIGNOR-263335 |
P42701 | Q9NPF7 | 0 | binding | up-regulates | 0.645 | Like il-12, il-23 binds to the il-12r subunit il-12rbeta1. | SIGNOR-87739 |
P61586 | Q9Y3M8 | 0 | gtpase-activating protein | down-regulates activity | 0.645 | We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2). | SIGNOR-260521 |
P51946 | P49336 | 0 | phosphorylation | down-regulates | 0.645 | Cdk8 phosphorylates mammalian cyclin h in the vicinity of its functionally unique amino-terminal and carboxy-terminal alpha-helical domains. This phosphorylation represses both the ability of tfiih to activate transcription and its ctd kinase activity | SIGNOR-82033 |
P35240 | Q13153 | 0 | phosphorylation | down-regulates | 0.645 | Merlin contains a c-terminal serine 518, which is phosphorylated both by p21-activated kinase (pak) and protein kinase a (pka) (shaw et al., 2001;kissil et al., 2002;xiao et al., 2002;alfthan et al., 2004). Phosphorylation at this site is predicted to result in a more open conformation incapable of inhibiting cell growth, | SIGNOR-159764 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.